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07 June 2022 | Story Prof Felicity Burt, Prof Dominique Goedhals and Dr Charles Kotzé
Prof Felicity Burt, Dr Charles Kotze and Prof Dominique Goedhals
From the left; Prof Felicity Burt, Dr Charles Kotzé and Prof Dominique Goedhals.

Opinion article by Prof Felicity Burt , Prof Dominique Goedhals , Division of Virology at the University of the Free State (UFS), and Dr Charles Kotzé, National Health Laboratory Service (NHLS), Universitas Academic Hospital.
The recent COVID-19 pandemic has certainly highlighted the importance of vigilance and awareness of emerging diseases with public health implications. The monkeypox virus has recently made headlines, after the detection of more than 200 cases in geographically distinct regions. On 13 May, the World Health Organisation (WHO) was notified of human cases of the monkeypox disease occurring in the United Kingdom, outside of the known endemic region.

Exported cases have been detected previously and usually occur sporadically. In contrast, within the past two weeks, human cases have been confirmed in at least 21 countries, including various European countries, the United Kingdom, Israel, the Canary Islands, Canada and the United States, and Australia. The initial case appears to have been a traveller from Nigeria. Sequence data may help to determine if there have been multiple exportations from West Africa. 

What is monkeypox and what do we know

What is monkeypox and what do we know about the aetiologic agent? Monkeypox is the name given to a disease caused by the monkeypox virus, a zoonotic pathogen endemic in Central and West Africa and responsible for cases of the disease in the endemic region, with occasional exported cases in travellers. The virus was initially identified in 1958 in monkeys housed at a research laboratory in Denmark, and the name monkeypox was derived from the appearance of lesions and the occurrence in monkeys. The first human case was identified 52 years ago in the Democratic Republic of the Congo. Since then, human monkeypox cases have been reported in several other Central and West African countries: Cameroon, the Central African Republic, Ivory Coast, the Democratic Republic of the Congo, Gabon, Liberia, Nigeria, Republic of the Congo, and Sierra Leone. The first monkeypox outbreak outside of Africa was in the United States of America in 2003 and was linked to contact with infected prairie dogs imported as exotic pets. Since then, there have been various small, contained outbreaks outside of Africa that have mostly been linked to the importation of the virus from African countries. 

The virus is related to the smallpox virus, which was eradicated in the 1970s by vaccination. Although belonging to the same family of viruses as the smallpox virus, the disease caused by monkeypox is less severe, with fewer fatalities.   Unlike smallpox, which carries a case fatality rate of 30%, the case fatality rate in monkeypox is low (estimated at 3-6% in more recent outbreaks).  There are two clades of the monkeypox virus: the West African clade and the Congo Basin (Central African) clade. In this outbreak, all of the cases have been linked to the West African clade of the monkeypox virus.

Transmission occurs from animal to human, and from human to human, through close contact with lesions, body fluids, and contaminated materials. The virus enters the body through the respiratory tract, mucous membranes, or broken skin.  The disease begins with non-specific symptoms such as fever, headache, muscle pains, and swollen lymph nodes. This is followed by the typical skin rash, which progresses through stages known as macules, then papules, vesicles, pustules, and lastly crusts or scabs. Lesions can also occur on mucous membranes such as the mouth, eye, and genital area.  The infectious period lasts through all stages of the rash, until all the scabs have fallen off. There are a number of other infectious and non-infectious conditions that need to be differentiated; therefore, individuals presenting with these symptoms will need to consult their doctor to determine whether a diagnosis of monkeypox needs to be considered. In the current outbreak, a number of the cases in the United Kingdom and Europe have been detected in men who have sex with men, during visits to sexual health clinics. This pattern of spread has not previously been described and it remains to be determined whether the spread has occurred through close person-to-person contact or through sexual transmission.  

Vaccination against smallpox virus offers 85% protection against monkeypox

To date, no cases have been detected in South Africa, but the recent global spread of the severe acute respiratory syndrome coronavirus 2 (SARS_CoV-2) highlights the ability of pathogens to spread. The National Institute for Communicable Diseases (NICD) in Johannesburg offers a specialised diagnostic service for the monkeypox virus, using molecular assays and electron microscopy. 

Vaccination against the smallpox virus is believed to offer 85% protection against monkeypox, hence older persons should have some protection; however, vaccination against smallpox was phased out globally following the eradication of smallpox during the 1970s. A more recently developed vaccine against monkeypox is available but has very limited availability.  No specific antivirals are available with proven efficacy in clinical trials.

While the monkeypox virus can be spread via the respiratory route, this occurs in the form of large droplets, rather than aerosol transmission, which is seen with SARS-CoV-2 (causing COVID-19). Aerosols are smaller particles that can remain suspended in the air for prolonged periods, facilitating the transmission of SARS-CoV-2. Monkeypox is therefore less contagious than COVID-19, as close contact is required for longer periods.  For this reason, many experts around the world predict that this outbreak will not spread like SARS-CoV-2. The importation of monkeypox to South Africa is a definite possibility, because South Africa is a significant economic and travel hub for Africa. Previous outbreaks of monkeypox in non-endemic areas have been interrupted by contact tracing and isolation, which was very effective in controlling further spread.  Heightened vigilance is therefore needed for the early detection of such cases.

News Archive

UFS study on cell development in top international science journal
2008-09-16

A study from the University of the Free State (UFS) on how the change in the packaging of DNA with cell development influenced the expression of genes, will be published in this week’s early edition of the prestigious international, peer-reviewed science journal, the Proceeding of the National Academy of Sciences of the USA (PNAS).

The PNAS journal has an impact factor of 10, which means that studies published in the journal are, on average, referred to by ten other scientific studies in a two year period. The South African Journal of Science, by comparison, has an impact factor of 0.7.

The UFS study, funded by the Wellcome Trust and the National Research Foundation (NRF), looked at how the change in the packaging of DNA with cell development influenced the expression of genes. It is very relevant to research on stem cells, an area of medicine that studies the possible use of undifferentiated cells to replace damaged tissue.

Prof. Hugh Patterton, of the Department of Microbial, Biochemical and Food Biotechnology at the UFS, who led the study, said: "We are extremely proud of this study. It was conceived in South Africa, it was performed in South Africa, the data were analysed in South Africa, and it was published from South Africa."

When a gene is expressed, the information encoded in the gene is used to manufacture a specific protein. In eukaryotes, which include humans, there is approximately 1m of DNA, containing the genes, in every cell. This length of DNA has to fit into a cell nucleus with a diameter of only about 10 micrometer. In order to fit the DNA into such a small volume, eukaryotic cells wrap their DNA onto successive protein balls, termed nucleosomes. Strings of nucleosomes, resembling a bead of pearls, is folded into a helix to form a chromatin fiber. The study from the UFS investigated how the binding of a specific protein, termed a linker histone, that binds to the length of DNA between nucleosomes, influenced the formation of the chromatin fiber and also the activity of genes.

"We found that the linker histone bound to chromatin in yeast, which we use as a model eukaryote, under conditions where virtually all the genes in the organism were inactive. It was widely believed that the binding of the linker histone caused the inactivation of genes. We studied the relationship between the amount of linker histone bound in the vicinity of each gene and the expression of that gene for all the genes in yeast, using genomic techniques. We made the surprising discovery that even through the linker histone preferentially bound to genes under conditions where the genes were shut off, this inactivation of genes was not caused by the binding of the linker histone and folding of the chromatin,” said Prof. Patterton.

He said: “Instead our data strongly suggested that the observed anti-correlation was due to the movement of enzymes along the DNA molecule, involved in processing the information in genes for the eventual manufacture of proteins. This movement of enzymes displaced the linker histones from the DNA. This finding now requires a rethink on aspects of how packaging of DNA influences gene activity."

Prof. Patterton said that his research group, using the Facility for Genomics and Proteomics as well as the Bioinformatics Node at the UFS, was currently busy with follow-up studies to understand how other proteins in nucleosomes affected the activities of genes, as well as with projects to understand how chemicals found in red wine and in green tea extended lifespan. "We are certainly having a marvelous time trying to understand the fundamental mechanisms of life, and the UFS is an exciting place to be if one was interested in studying life at the level of molecules," he said.


Media Release
Issued by: Lacea Loader
Assistant Director: Media Liaison
Tel: 051 401 2584
Cell: 083 645 2454
E-mail: loaderl.stg@ufs.ac.za  
18 September 2008
 

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